ArticleThe Journal of clinical investigation2012
Endothelial HIF-2α regulates murine pathological angiogenesis and revascularization processes.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 131 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
131 citing papers in PubMed, 193 citations in OpenAlex.
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- The metabolic plasticity of cancer stem cells: bidirectional crosstalk with organ-resident cells.Experimental & molecular medicine · 2026Review
- The role and mechanism of 3D-printed hydrogel-CGF/PLGA composite polymer in promoting skin burn healing.Journal of molecular histology · 2026Article
- HIF-mediated hierarchical hypoxic adaptation, a novel paradigm in heart failure pathogenesis: is there a role for targeted therapies?Frontiers in pharmacology · 2026Review
- Arteriolar angiogenesis: implications in anti-angiogenic immunotherapy for pancreatic cancers.Cytokine & growth factor reviews · 2025Review
- Biological Regulation of HIF-1α and Its Role in Therapeutic Angiogenesis for Treatment of Ischemic Cardiovascular Disease.International journal of molecular sciences · 2025Review
- Low Wall Shear Stress Promotes Atheroma via Arterial Iron Accumulation.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- HIF-2α Interaction with Ataxin-10 Enhances HIF-2α Binding to Its Target Gene Promoters.International journal of molecular sciences · 2025Article
- Multiomics Analysis of Skeletal Muscle Identifies Dysregulation of Hypoxia-Induced Genes in Peripheral Artery Disease.Journal of the American Heart Association · 2025Article
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- Warburg-like Metabolic Reprogramming in Endometriosis: From Molecular Mechanisms to Therapeutic Approaches.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Limning of HIF-2 and HIF-3 in the Tumor Microenvironment: Developing Concepts for the Treatment of Hypoxic Cancer.Current molecular medicine · 2025Review
- Hypoxia and collagen deposition in the kidneys infected with Acanthamoeba sp.Scientific reports · 2024Article
- 4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury in mice.Cell death discovery · 2024Article
- EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites Through Endothelial Fatty Acid Uptake.Circulation research · 2024Article
- 4-aminopyridine attenuates inflammation and apoptosis and increases angiogenesis to promote skin regeneration following a burn injury.Research square · 2024Article
- Endothelial HIF2α suppresses retinal angiogenesis in neonatal mice by upregulating NOTCH signaling.Development (Cambridge, England) · 2024Article
- Aerobic glycolysis of vascular endothelial cells: a novel perspective in cancer therapy.Molecular biology reports · 2024Review
71 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
Abstract
Localized tissue hypoxia is a consequence of vascular compromise or rapid cellular proliferation and is a potent inducer of compensatory angiogenesis. The oxygen-responsive transcriptional regulator hypoxia-inducible factor 2α (HIF-2α) is highly expressed in vascular ECs and, along with HIF-1α, activates expression of target genes whose products modulate vascular functions and angiogenesis. However, the mechanisms by which HIF-2α regulates EC function and tissue perfusion under physiological and pathological conditions are poorly understood. Using mice in which Hif2a was specifically deleted in ECs, we demonstrate here that HIF-2α expression is required for angiogenic responses during hindlimb ischemia and for the growth of autochthonous skin tumors. EC-specific Hif2a deletion resulted in increased vessel formation in both models; however, these vessels failed to undergo proper arteriogenesis, resulting in poor perfusion. Analysis of cultured HIF-2α-deficient ECs revealed cell-autonomous increases in migration, invasion, and morphogenetic activity, which correlated with HIF-2α-dependent expression of specific angiogenic factors, including delta-like ligand 4 (Dll4), a Notch ligand, and angiopoietin 2. By stimulating Dll4 signaling in cultured ECs or restoring Dll4 expression in ischemic muscle tissue, we rescued most of the HIF-2α-dependent EC phenotypes in vitro and in vivo, emphasizing the critical role of Dll4/Notch signaling as a downstream target of HIF-2α in ECs. These results indicate that HIF-1α and HIF-2α fulfill complementary, but largely nonoverlapping, essential functions in pathophysiological angiogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.